Cognition in Essential Tremor: A Neuroimaging and Biomarker Study

项目总结/摘要 特发性震颤（ET）是世界上最常见的神经系统疾病之一。除了有 作为双侧运动性震颤的标志性特征，患有原发性震颤的个体通常表现为轻度认知障碍， 主要表现为执行障碍并被视为与异常有关的变化 大脑皮层网络中的一个重要部分。然而，越来越多的证据表明， 超越了前执行域，流行病学研究表明，ET患者在 与年龄匹配的同龄人相比，患痴呆症的风险增加。之前的研究由 申请人鉴定了一个ET患者亚组，其具有更广泛的认知缺陷，包括记忆力差。这 这就提出了一个问题，即是否有更广泛的神经变化发生在外部， 小脑网络在至少一个子集的个人与ET。事实上，神经成像的初步发现 神经病理学研究表明，ET和阿尔茨海默病之间可能存在联系。 进一步的研究有必要探索这种联系，包括检查与认知功能相关的生物标志物。 下降本研究的总体目标是更好地了解ET中认知的神经相关性。 这项研究的目的是：1）使用数据驱动（聚类分析） 方法和全面的神经认知评估，2）确定是否不同的认知概况， ET在结构性脑变化中变化（即，游离水，体积），和3）探索是否血浆获得性 与阿尔茨海默病相关的生物标志物在具有记忆相关的ET个体中升高 相对于那些没有改变的人。拟议研究的创新特点包括确定 具有不同类型认知缺陷的ET个体的认知神经解剖学相关性， 游离水成像和血浆生物标记物作为早期肿瘤的敏感和有效的体内标记物的用途 神经变性这项研究的发现可能会增加目前对自然的理解， ET中认知变化的异质性，有可能提供有关 ET和痴呆症拟议项目还将为申请人提供额外的培训 包括在她的博士学位里程序.具体而言，培训目标将包括1）磁性的实践培训 共振成像数据处理和分析，重点是结构（T1）和自由水成像，2） 年龄相关神经系统认知功能障碍的神经基础和机制课程 3）与阿尔茨海默病和痴呆相关的血浆生物标志物的教学法，4）与阿尔茨海默病和痴呆相关的血浆生物标志物的训练， 使用编程语言进行统计计算和神经成像处理，5）开发 专业和职业技能。申请人得到强大的研究环境的支持， 完成拟议项目所需的资源和基础设施，以及富有成效的指导团队 在建议的研究领域具有特定的专业知识。

PROJECT SUMMARY/ABSTRACT Essential tremor (ET) is among the most prevalent neurological disorders in the world. In addition to the hallmark feature of bilateral kinetic tremor, individuals with essential tremor often present with mild cognitive changes that have been primarily characterized as dysexecutive and viewed as being related to abnormalities in cerebello-cortical networks. However, growing evidence suggests that cognitive difficulties can extend beyond the frontal-executive domain, and epidemiological research has shown that individuals with ET are at an increased risk for developing dementia compared to age-matched peers. Prior research conducted by the applicant identified a subgroup of ET patients who had broader cognitive deficits, including poor memory. This gives rise to the question of whether there may be more widespread neural changes occurring outside cerebellar networks in at least a subset of individuals with ET. Indeed, preliminary findings from neuroimaging and neuropathological studies have suggested that there may be a link between ET and Alzheimer’s disease. Further research is warranted to explore this link, including examining biomarkers associated with cognitive decline. The overall goal of the current study is to better understand the neural correlates of cognition in ET. The proposed study aims to 1) identify cognitive phenotypes in ET using a data-driven (cluster analytic) approach and comprehensive neurocognitive assessment, 2) determine whether different cognitive profiles in ET vary in structural brain changes (i.e., free-water, volume), and 3) to explore whether plasma-acquired biomarkers associated with Alzheimer’s disease are elevated in individuals with ET who have memory-related changes relative to those who do not. Innovative features of the proposed study include determining neuroanatomical correlates of cognition in individuals with ET who have different types of cognitive deficits and use of free-water imaging and plasma biomarkers as sensitive and powerful in vivo markers of early neurodegeneration. Findings from this study may increase current understanding about the nature and heterogeneity of cognitive changes in ET, with the potential to provide further information on the link between ET and dementia. The proposed project will also provide the applicant with additional training beyond that included in her Ph.D. program. Specifically, training goals will include 1) hands-on training in magnetic resonance imaging data processing and analysis with emphasis on structural (T1) and free-water imaging, 2) coursework in neural bases and mechanisms underlying cognitive dysfunction in age-related neurological disorders, 3) didactics in plasma biomarkers associated with Alzheimer’s disease and dementia, 4) training in using programming languages for statistical computing and neuroimaging processing, 5) development of professional and career skills. The applicant is supported by a strong research environment with the necessary resources and infrastructure for completion of the proposed project, as well as a productive mentoring team with specific expertise in the proposed areas of study.